A joint study with Drs. Basil and Hana Golding (CBER, FDA) has continued to follow a lead toward developing a therapeutic vaccine for treating patients in advanced stages of HIV infection whose immune systems have already been compromised. Our approach is based on the use of heat-killed Brucella abortus organisms (BA) as an adjuvant and combined T cell-dependent and -independent (type I) carrier. Immune responses to covalent conjugates of BA and HIV-derived peptides and recombinant proteins have been studied in normal and T cell-depleted mice. This carrier characteristically gives strong Th1-type responses and cytokine profiles, with potentially functional humoral and cellular immune responses, even in mice without a functioning level of CD4+ T cells. We are also preparing and evaluating covalent conjugates of HIV peptides and the purified lipopolysaccharide from B. abortus. These conjugates are less Th1-directing, and we will be seeking ways of further strengthening this type of response and cellular immunity through the use of specially designed delivery vehicles.